Table 1. Effects of AS703026 on CD138-purified tumor cells from patients with relapsed/refractory MM.
| Patient | RAS mutation | BRAF mutation | % Inhibition at 200 nM | IC50 (nM) |
|---|---|---|---|---|
| MM1 | N- (G12T) | - | 57% | 200 |
| MM2 | - | - | 75% | 2 |
| MM3 | - | - | 60% | < 200 |
| MM4 | - | - | 79%* | < 20 |
| MM5 | - | D594G | 76%* | < 20 |
| MM6 | - | - | 61%* | < 20 |
| MM7 | K- (G12A) | - | 51% | 20 |
| MM8a | N- (G13D) | - | 95% | 20 |
| MM9 | - | - | 98% | 2-20 |
| MM10 | - | - | 98% | 2-20 |
| MM11 | N- (R97G) | V600E | 99% | < 20 |
| MM12 | - | - | 64%* | < 20 |
| MM13 | - | - | 73% | 20-200 |
| MM14 | N- (Q61K) | - | 30%* | >200 |
| MM15 | - | - | 8%* | >200 |
| MM16 | K- (G12A, A61G) | - | 21% | >2000 |
| MM17 | - | - | 23% | >2000 |
| MM18 | - | - | 74% | 20-200 |
MM patient cells were purified by positive selection with CD138 microbeads, treated in vitro with AS703026 for 5 days and then analyzed by cytotoxicity assays using [3H] update (MM1-18) and MTT assays (MM1-8).
-, wild type of the gene;
*
% Inhibition at 20 nM drug;
MM8a: a plasma cell leukemia